TY - JOUR
T1 - New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis
AU - Inoue, Norimitsu
AU - Hess, Karl D.
AU - Moreadith, Randall W.
AU - Richardson, Laura L.
AU - Handel, Mary Ann
AU - Watson, Mark L.
AU - Zinn, Andrew R.
N1 - Funding Information:
We thank R. Schultz for a mouse testis cDNA library; N. Miura for help with in situ hybridization; M. Brown, J. Goldstein, J. Holder and R. Prueitt for helpful comments; and B. Ouyang for technical assistance. This work was supported by the UT Southwestern Program for Excellence in Postgraduate Research (M.L.W. and A.R.Z.) and NIH grant HD31376 (M.A.H.).
PY - 1999
Y1 - 1999
N2 - Mammalian spermatogenesis is a complex developmental process. The analysis of mouse mutations has provided insight into biochemical pathways required for completion of this process. We previously described the autosomal recessive mouse morc(TgN(Tyr)1Az) (microrchidia) mutation, a serendipitous transgenic insertional mutation which causes arrest of spermatogenesis prior to the pachytene stage of meiosis prophase I. We now report the molecular characterization of the morc locus and positional cloning of a gene disrupted by the morc(TgN(Tyr)1AZ) mutation. This gene, which we term Morc, encodes a 108 kDa protein expressed specifically in male germ cells. The transgene integrated within the first intron of Morc and was accompanied by an intragenic deletion of ~ 13 kb of genomic sequences, removing exons 2-4 and abrogating expression of the wild-type transcript. Analysis of the MORC protein sequence revealed putative nuclear localization signals, two predicted coiled-coil structural motifs and limited homology to GHL (GyraseB, Hsp90, MutL) ATPase. Epitope-tagged MORC protein expressed in COS7 cells localized to the nucleus. We also cloned the human MORC homolog and show that it too is testis-specific, but closely related human genes are transcribed in multiple somatic tissues. Homologous proteins are also present in zebrafish, nematodes, slime mold and plants. Thus, cloning of Morc defines a novel gene family whose members are likely to serve important biological functions in both meiotic and mitotic cells of multicellular organisms.
AB - Mammalian spermatogenesis is a complex developmental process. The analysis of mouse mutations has provided insight into biochemical pathways required for completion of this process. We previously described the autosomal recessive mouse morc(TgN(Tyr)1Az) (microrchidia) mutation, a serendipitous transgenic insertional mutation which causes arrest of spermatogenesis prior to the pachytene stage of meiosis prophase I. We now report the molecular characterization of the morc locus and positional cloning of a gene disrupted by the morc(TgN(Tyr)1AZ) mutation. This gene, which we term Morc, encodes a 108 kDa protein expressed specifically in male germ cells. The transgene integrated within the first intron of Morc and was accompanied by an intragenic deletion of ~ 13 kb of genomic sequences, removing exons 2-4 and abrogating expression of the wild-type transcript. Analysis of the MORC protein sequence revealed putative nuclear localization signals, two predicted coiled-coil structural motifs and limited homology to GHL (GyraseB, Hsp90, MutL) ATPase. Epitope-tagged MORC protein expressed in COS7 cells localized to the nucleus. We also cloned the human MORC homolog and show that it too is testis-specific, but closely related human genes are transcribed in multiple somatic tissues. Homologous proteins are also present in zebrafish, nematodes, slime mold and plants. Thus, cloning of Morc defines a novel gene family whose members are likely to serve important biological functions in both meiotic and mitotic cells of multicellular organisms.
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U2 - 10.1093/hmg/8.7.1201
DO - 10.1093/hmg/8.7.1201
M3 - Article
C2 - 10369865
AN - SCOPUS:0032776555
SN - 0964-6906
VL - 8
SP - 1201
EP - 1207
JO - Human molecular genetics
JF - Human molecular genetics
IS - 7
ER -